Comparison of IMC-2 alone and IMC-2 and Paxlovid® shows substantial short and long-term efficacy in reducing symptoms of Long COVID with combination therapy: a case series

Introduction Long COVID (LC), an infection-associated chronic illness (IACI) with no currently approved treatments. In order to address SARS-CoV-2 persistence and herpesvirus reactivation, which have been implicated as drivers of LC, sustained use of antiviral combinations may have utility in treating patients with the illness. Methods We studied a convenience sample of patients engaged in an extended course of a combination of antiviral medications, either IMC-2 Only (IO) or IMC-2 with the addition of 15 days of Paxlovid (IP), prescribed off-label, to people with LC being treated at an outpatient clinic. The Patient Global Impression of Change (PGIC) was used to measure response to the therapy over time, with a primary focus on fatigue symptom reporting and a secondary focus on brain fog and dysautonomia symptoms. In addition, visual analogue scales (VAS) were used to track perceived symptom improvements. Results Twenty-seven people with LC were approached for treatment, of whom 24 completed one or both protocols. Twelve were treated with IO and twelve were given the continuous IP combination. A reduction in fatigue, reported on the PGIC, was observed in both groups, but those who received IP experienced a statistically significant improvement compared to those who received IO (p < 0.0001). Similarly, using a VAS, patients reported an average 55.3% (p < 0.0001) greater reduction of fatigue in the IP group, compared with the IO group. Patients who completed the IP intervention demonstrated significant durability in their clinical benefit, with reported symptom improvements remaining consistent at 120-, 305- and 731-day follow-ups. Discussion This small, open-label case series provides pilot evidence to support the need for a larger trial of combination antivirals for people living with LC. Based on these results a larger, controlled trial of IMC-2 paired with Paxlovid should be conducted.